Prenatal Diagnosis of a Lethal Multiple Pterygium Syndrome Type II

Abstract

Advances in ultrasound technology and sonographer’s experience lead to the description of many rare syndromes and malformations through prenatal diagnosis. Diaphragmatic hernia is a rather common malformation but can be an indicator of different syndromes. We report the prenatal diagnosis of lethal multiple pterygium syndrome type II which has been established in the 34th week of pregnancy. The sonographically detectable symptoms consisted of polyhydramnios, hygroma colli, diaphragmatic hernia, scoliosis, short forearms, hypokinesia of the fetus and pterygia over the large joints. Labour was induced in the 34th week of pregnancy; the neonate died shortly after vaginal delivery as a result of the pulmonary hypoplasia. A multidisciplinary approach in prenatal assessment may help to clarify difficult diagnostic problems and may be of direct benefit for the pregnant patient.

Genetic causes of congenital diaphragmatic hernia

“…One or more cases of the following autosomal dominant conditions have all been described with CDH: Kabuki syndrome with a mutation in KMT2D/MLL2 [80], Baller–Gerold/Saethre–Chötzen with a mutation in TWIST [81], Apert syndrome with craniosynostosis and an FGFR2 mutation [82], SHORT syndrome with a BMP4 mutation [83], tuberos sclerosis type 2 with a TSC2 mutation [84], Beckwith–Wiedemann syndrome with a paternally inherited der(4)t t(4;11)(q33;p14) [85], C-trigonocephaly [86], and multiple pterygium syndrome [87] without identified causes.…”

Examination of FGFRL1 as a candidate gene for diaphragmatic defects at chromosome 4p16.3 shows that Fgfrl1 null mice have reduced expression of Tpm3, sarcomere genes and Lrtm1 in the diaphragm

“…For training or comparison genes, we provided the genes previously determined to be mutated in human syndromes with CDH, including WT1, GPC3, CHD7, NIPBL, EFNB1, LRP2, DLL3, FBN1, CHRNG, STRA6 and HCCS (Entezami et al 1998; Bulman et al 2000; Li et al 2001; Revencu et al 2004; Vissers et al 2004; Vasudevan et al 2006; Wimplinger et al 2006; Kantarci et al 2007; Pasutto et al 2007; Antonius et al 2008), and genes known to be associated with diaphragmatic defects in null mice, including Fog2, Slit3, Robo1 and Lox (Hornstra et al 2003; Yuan et al 2003; Ackerman et al 2005). We used all of the Ref Seq genes from chromosome 4, nucleotides 1–2,406,426 (numbering according to hg 18; UCSC Genome Browser, http://genome.ucsc.edu) as the candidate genes, using the location of D4S43 to provide the outer boundary of the test region (Casaccia et al 2006; UCSC genome browser http://genome.ucsc.edu/).…”

Genetics of Congenital Diaphragmatic Hernia

“…The inheritance is autosomal recessive (Entezami et al, 1998;Morgan et al, 2006). The prevalence of this syndrome has not been described.…”